sildenafil-citrate and Adenocarcinoma

To evaluate the long-term effect and safety of sildenafil citrate for the treatment of erectile dysfunction after radical prostatectomy (RP).. The study consisted of 91 patients with erectile dysfunction from our institution who received oral sildenafil citrate after RP. We surveyed these patients using a self-administered questionnaire during the first year of sildenafil citrate use to determine treatment satisfaction, patient compliance, and safety. Those who had responded positively to the drug were surveyed again 3 years later (n = 48). Sildenafil citrate was prescribed at a dose of 50 mg and increased to 100 mg if needed. Data were collected from a self-administered questionnaire using the abridged five-item version of the International Index of Erectile Function questionnaire, referred to as the Sexual Health Inventory of Men, and the Erectile Dysfunction Inventory of Treatment Satisfaction. The patients were stratified according to the type of nerve-sparing (NS) RP procedure they underwent: bilateral NS, unilateral NS, and non-NS.. At 3 years, 31 (71%) of the 43 patients who had returned the second surveys were still responding to sildenafil. Of these 31 respondents, 10 (31%) had augmented their dose from 50 to 100 mg. The dropout rate was 27%; 6 of 12 had discontinued because of the return of natural erections, 5 because of a loss of efficacy, and 1 because his spouse had died. No differences were found in the 1-year and 3-year five-item International Index of Erectile Function (Sexual Health Inventory of Men) and Erectile Dysfunction Inventory of Treatment Satisfaction scores between the NS groups. The most common side effects at 3 years were headache (12%), flushing (10%), and blue or blurred vision (2%). No patient discontinued the drug at 3 years because of side effects.. The results of this study indicate that the vast majority of patients with erectile dysfunction after RP who initially respond to sildenafil continue to do so at 3 years and are satisfied and compliant with the treatment regimen.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Adenocarcinoma; Adult; Aged; Cyclic Nucleotide Phosphodiesterases, Type 5; Drug Evaluation; Erectile Dysfunction; Follow-Up Studies; Health Surveys; Humans; Male; Middle Aged; Patient Dropouts; Patient Satisfaction; Penis; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Prostatectomy; Prostatic Neoplasms; Purines; Safety; Sildenafil Citrate; Sulfones; Surveys and Questionnaires; Treatment Outcome

To determine the efficacy of sildenafil citrate (Viagra) in patients with erectile dysfunction after three-dimensional conformal external beam radiotherapy for prostate cancer.. Sixty patients treated with radiotherapy for prostate cancer at least 6 months previously, complaining of erectile dysfunction, and not using nitrates were entered into a double-blind, placebo-controlled, crossover study lasting 12 weeks. They received 50 mg of sildenafil or placebo for 2 weeks; at week 2, the dose was increased to 100 mg in the case of an unsatisfactory erectile response. At week 6, patients crossed over to the alternative treatment. Patients were then allowed to enter a 6-week open-label phase using 50 mg of sildenafil in the first 2 weeks, increasing the dose to 100 mg in the case of an insufficient erectile response in the following 4 weeks. Data were collected before trial entry (baseline evaluation) and every 2 or 4 weeks using the International Index of Erectile Function questionnaire. Any side effects were recorded. Two years later, all patients were approached by mail to evaluate their current sexual functioning and possible use of sildenafil.. All patients completed the double-blind, crossover study. For nearly all the International Index of Erectile Function questions, sildenafil caused a significant increase in mean scores from baseline. Placebo had no effect. Seventy-seven percent entered the open-label phase; they were the better responders in the double-blind phase. Sildenafil was as equally effective as in the double-blind phase. The side effects were mild or moderate and significantly decreased in the open-label period. Two years after trial entry, 24% still used sildenafil.. Sildenafil is relatively effective in patients with erectile dysfunction after three-dimensional conformal external beam radiotherapy for prostate cancer. New drugs and combination therapies are needed to improve outcome.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Adenocarcinoma; Aged; Cross-Over Studies; Cyclic Nucleotide Phosphodiesterases, Type 5; Double-Blind Method; Drug Evaluation; Erectile Dysfunction; Follow-Up Studies; Health Surveys; Humans; Male; Middle Aged; Patient Satisfaction; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Prostatic Neoplasms; Purines; Radiation Injuries; Radiotherapy, Conformal; Safety; Sildenafil Citrate; Sulfones; Surveys and Questionnaires; Treatment Outcome

To assess the long-term sexual potency and attrition in sexual function after iodine-125 ((125)I) seed radiotherapy and the effect of sildenafil on radiation-induced erectile dysfunction (ED).. This prospective study consisted of 86 sexually active patients (mean age 63.5 +/- 7.7 years) who underwent (125)I seed implantation from 1997 to 1999 to treat low-volume prostate cancer (prostate-specific antigen less than 10 ng/mL, Gleason score 6 or less, stage T1-T2). All patients were followed up every 6 to 8 months for 4 years. Patients prescribed sildenafil citrate for ED completed the abridged five-item version of the International Index of Erectile Function (IIEF) and the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaires.. The median follow-up was 49.7 months (range 36 to 66). Of 86 patients, 43 (50%) did not initiate drug therapy; and only 36 (83.7%) of the 43 were interviewed at 4 years. Twenty-three (63.8%) of the 36 patients had erections sufficient for vaginal penetration, with a total mean +/- SD IIEF-5 score of 15.76 +/- 1.13. The other 50% (43 of 86) initiated sildenafil citrate for treatment of ED after seed implantation, with a minimal follow-up of 6 months. At 4 years, 32 (74%) of the 43 were responding positively to sildenafil citrate, with a total IIEF-5 score of 18.3 +/- 1.2. The mean EDITS +/- SD score was 76.5 +/- 3.2, and the spousal satisfaction rate was 72% (31 of 43). The dropout rate was 37% (16 of 43); 10 (63%) of the 16 discontinued because of a lack of efficacy, 3 (19%) because of a return of natural erections sufficient for vaginal penetration, and 3 (19%) discontinued because of side effects (headaches).. ED is a major long-term issue after (125)I seed radiotherapy, with a long-term potency rate of 29%. Sildenafil citrate improves erections in most patients after (125)I seed implantation.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Brachytherapy; Erectile Dysfunction; Follow-Up Studies; Headache; Humans; Iodine Radioisotopes; Male; Middle Aged; Patient Satisfaction; Piperazines; Prospective Studies; Prostatic Neoplasms; Purines; Severity of Illness Index; Sexual Partners; Sildenafil Citrate; Sulfones; Vasodilator Agents

To ascertain the efficacy of sildenafil citrate (Viagra) in patients with erectile dysfunction (ED) either before or after prostate brachytherapy by an open-label, nonrandomized study.. Sixty-two patients who underwent prostate brachytherapy between March 1995 and July 1998, had ED either before or after brachytherapy, and were interested in treatment with sildenafil comprised the patient population. Clinical and treatment parameters evaluated for medication efficacy included patient age at brachytherapy and at medication administration, hypertension, diabetes, smoking history, onset of ED, potency status before implant, frequency of intercourse before brachytherapy (if potent), use of neoadjuvant hormonal manipulation, use of moderate dose external beam radiation therapy before implantation, choice of isotope, V100 (the percentage of the prostate volume receiving at least 100% of the prescribed minimal peripheral dose), and sildenafil dose.. Fifty (80.6%) of 62 patients responded favorably to sildenafil. None of the treatment parameters predicted medication failure, and among the clinical parameters, only diabetes predicted failure (3 of 5) and only with borderline statistical validity (P = 0.046).. Our results suggest brachytherapy-induced impotence is as amenable to sildenafil treatment as ED from other causes. In addition, our 80.6% success rate is comparable to reported results for patients who underwent bilateral nerve-sparing radical prostatectomy and significantly better than patients who underwent unilateral nerve-sparing or non-nerve-sparing approaches.

Topics: Adenocarcinoma; Aged; Brachytherapy; Erectile Dysfunction; Humans; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Prostatic Neoplasms; Purines; Sildenafil Citrate; Sulfones

Topics: Adenocarcinoma; Chemotherapy, Adjuvant; Contraindications; Humans; Libido; Male; Middle Aged; Quality of Life; Sildenafil Citrate; Stomach Neoplasms

It has been demonstrated that aggressive in situ tumor destruction (ablation) could lead to the release of tumor antigens, which can stimulate anti-tumor immune responses. We developed an innovative method of tumor ablation based on intratumoral alpha-irradiation, diffusing alpha-emitters radiation therapy (DaRT), which efficiently ablates local tumors and enhances anti-tumor immunity. In this study, we investigated the anti-tumor potency of a treatment strategy, which combines DaRT tumor ablation with two approaches for the enhancement of anti-tumor reactivity: (1) neutralization of immunosuppressive cells such as regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) and (2) boost the immune response by the immunoadjuvant CpG. Mice bearing DA3 mammary adenocarcinoma with metastases were treated with DaRT wires in combination with a MDSC inhibitor (sildenafil), Treg inhibitor (cyclophosphamide at low dose), and the immunostimulant, CpG. Combination of all four therapies led to a complete rejection of primary tumors (in 3 out of 20 tumor-bearing mice) and to the elimination of lung metastases. The treatment with DaRT and Treg or MDSC inhibitors (without CpG) also resulted in a significant reduction in tumor size, reduced the lung metastatic burden, and extended survival compared to the corresponding controls. We suggest that the therapy with DaRT combined with the inhibition of immunosuppressive cells and CpG reinforced both local and systemic anti-tumor immune responses and displayed a significant anti-tumor effect in tumor-bearing mice.

Topics: Ablation Techniques; Adenocarcinoma; Alpha Particles; Animals; Antigens, Neoplasm; Brachytherapy; Breast Neoplasms; Cell Growth Processes; Cell Line, Tumor; Combined Modality Therapy; Cyclophosphamide; Female; Humans; Mice; Mice, Inbred BALB C; Myeloid-Derived Suppressor Cells; Oligodeoxyribonucleotides; Sildenafil Citrate; T-Lymphocytes, Regulatory; Tumor Burden

Patients with recurrent ischemic priapism have historically been treated with anti-androgen therapy due to the limited available evidence for more targeted therapies to treat the underlying pathophysiologic mechanisms of this condition. We report a case in which anti-androgen therapy caused significant adverse side effects and likely masked this patient's elevated prostate-specific antigen (PSA) levels, which adversely impacted the timely diagnosis and treatment of his prostate cancer.. A 69-year-old man treated with anti-androgens for priapism initially developed unwanted anti-androgenic side effects such as gynecomastia, erectile dysfunction, and decreased libido. After decreasing his anti-androgen dosage and starting a specified regimen of phosphodiesterase type 5 inhibitor therapy, his serum PSA levels were found to be elevated. He was subsequently diagnosed with adenocarcinoma of the prostate and underwent a radical prostatectomy with the pathologic finding of high-grade, locally progressive disease.. Anti-androgen therapy carries significant complication risks, including the potential to alter the diagnosis and treatment of prostate cancer. Clinicians administering this therapy for priapism management should be aware of these possible risks.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Anilides; Delayed Diagnosis; Humans; Male; Nitriles; Phosphodiesterase 5 Inhibitors; Piperazines; Priapism; Prostate-Specific Antigen; Prostatic Neoplasms; Purines; Secondary Prevention; Sildenafil Citrate; Sulfones; Tosyl Compounds

Chronic inflammation, recruitment of myeloid-derived cells, and perturbation of the arginine metabolism have been all proposed as mechanisms favoring prostate carcinogenesis and tumor immunoescape. Objective of this study was to evaluate whether accumulation of CD11b(+)Gr1(+) cells, also defined myeloid-derived suppressor cells, occur in mice affected by transplantable or spontaneous prostate cancer (PC). We also investigated whether N(G) nitro-L-arginine methyl ester (L-NAME) and sildenafil, both modulators of the arginine metabolism, restrain tumor growth and restore tumor-specific immunity.. Wild-type C57BL/6 mice bearing TRAMP-C1 PC and transgenic adenocarcinoma of the mouse prostate (TRAMP) mice were treated with vehicle, L-NAME or sildenafil, and evaluated for CD11b(+) cells accumulation in the blood, several organs, and the tumor mass and for disease progression.. CD11b(+)Gr1(high), CD11b(+)Gr1(int), and CD11b(+)Gr1(-) cells differently accumulated in different organs and especially in the tumor of the two mouse models. L-NAME and sildenafil impaired the immunosuppressive function of CD11b(+) cells in both models and restrained TRAMP-C1 growth, but they neither break tumor-specific immune tolerance nor limit tumor progression in TRAMP mice.. Collectively, our results emphasize substantial differences in tumor-induced alteration of myelopoiesis and sensitivity to modulators of the arginine metabolism between a transplantable and a spontaneous model of PC. They also suggest that perturbation of the arginine metabolism is dispensable for PC progression and the associated T-cell tolerance.

Topics: Adenocarcinoma; Animals; Arginine; CD11b Antigen; Cell Proliferation; Disease Progression; Immune Tolerance; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Myelopoiesis; NG-Nitroarginine Methyl Ester; Piperazines; Prostatic Neoplasms; Purines; Sildenafil Citrate; Sulfones; T-Lymphocytes; Tumor Cells, Cultured

Our institution previously described a surgical technique for preservation of accessory pudendal arteries at radical retropubic prostatectomy. Since then, we have expanded our experience. We now report our refinements in the surgical technique, illustrated with video, and the influence of accessory artery preservation on the recovery of sexual function after radical retropubic prostatectomy (RRP).. Between 1987 and 2003, 2399 potent men underwent RRP. Of the 2399 men, 84 (4%) were identified with accessory pudendal arteries. Of the 84 men, 52, who underwent bilateral nerve-sparing surgery, were available for evaluation. We identified a control population, without accessory pudendal arteries, who were matched for age, stage, and neurovascular bundle status. Potency was defined as the ability to achieve unassisted intercourse with or without the use of sildenafil. In a Cox proportional hazards model, the effect of artery preservation increased the likelihood of potency more than twofold (relative risk 2.65; 95% confidence interval 1.11 to 6.32; P = 0.028). Kaplan-Meier analysis showed a significantly shorter median time to regain potency among those with artery preservation, 6 versus 12 months (P = 0.020).. Preservation of accessory pudendal arteries may favorably influence the recovery of sexual function and interval to recovery after RRP.

Topics: Adenocarcinoma; Arteries; Cohort Studies; Erectile Dysfunction; Humans; Life Tables; Male; Middle Aged; Penis; Piperazines; Postoperative Complications; Proportional Hazards Models; Prostatectomy; Prostatic Neoplasms; Purines; Sildenafil Citrate; Sulfones; Treatment Outcome

We emphasize the good results obtained by authors of the United States of North America and Europe using prostate brachytherapy in the treatment of localized prostate cancer.. We report 50 patients with stage T1c-T2c treated during the last twenty one months (September 2000, June 2001). Two groups were made--according to Gleason, PSA, local infiltration and percentage of tumor volume in the Biopsy--in low and high risk patients. We report the methodology used in the surgical procedure.. We found the nadir of PSA was 0.5-1 in seven patients followed during eighteen months, and fifteen patients followed during twelve months. We had a failure in two patients. A reference is made about two patients with previously TURP and one with open prostatectomy, with very good post-operative results. Secondary effects are essentially irritative symptoms, well controlled by medical treatment. Four patients had acute urinary retention, one of them persistent. Normal erections were found in thirty five patients, and partial in fifteen, which had a very good respond to Sildenafil. Four cases had partial incontinence, currently only one persist during sleep.. We have had very good results during the first twenty one months of treatment of cancer of the prostate with brachytherapy. In our opinion the procedure is a very valid option of treatment for this disease.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Brachytherapy; Combined Modality Therapy; Disease-Free Survival; Erectile Dysfunction; Hematuria; Humans; Iodine Radioisotopes; Male; Middle Aged; Piperazines; Prospective Studies; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Purines; Radiopharmaceuticals; Remission Induction; Sildenafil Citrate; Sulfones; Transurethral Resection of Prostate; Treatment Outcome; Urinary Incontinence; Urination Disorders; Vasodilator Agents

To retrospectively evaluate the relationship between the radiation dose to the bulb of the penis and the development of erectile dysfunction (ED) in patients undergoing permanent prostate brachytherapy without external beam radiation therapy.. Twenty-three men who developed ED after transperineal ultrasound-guided permanent prostate brachytherapy for clinical T1/T2 adenocarcinoma of the prostate gland were paired with 23 similar men who maintained potency after implantation. Potency was defined as an erection sufficient for vaginal penetration. The mean and median follow-up for the entire group was 34.6 +/- 13.7 months and 32.8 months, respectively. Patients were implanted with either (125)I (145 Gy TG-43) or (103)Pd (115 Gy, pre-NIST-99). No patient received external beam radiation therapy either before or after brachytherapy. The bulb of the penis was outlined at 0.5-cm intervals on the Day 0 postimplant CT scan. The radiation dose distribution to the bulb of the penis was defined in terms of the minimal dose delivered to 25%, 50%, 70%, 75%, 90%, and 95% of the bulb (D(25), D(50), D(70), D(75), D(90), and D(95)).. The radiation dose delivered to the bulb of the penis in men with postbrachytherapy-induced ED was statistically greater for all evaluated dosimetric parameters (D(25), D(50), D(70), D(75), D(90), and D(95)). Multivariate analysis indicated that dose to the bulb of the penis and patient age at the time of implant were predictive of postimplant ED, whereas choice of isotope had no effect. Among potent patients, 19/23 had D(50) < or = 40% of prescribed minimal peripheral dose, whereas for the impotent patients, 19/23 had D(50) >40% of the minimal peripheral dose. Of the impotent patients, 17 utilized sildenafil, with 15 experiencing a favorable response (88%).. Our data suggest that prostate brachytherapy-induced impotence is highly correlated with the radiation dose delivered to the bulb of the penis. With Day 0 dosimetric evaluation, the radiation dose delivered to 50% of the bulb of the penis should be maintained at 50 Gy or less to maximize post-treatment potency. Fortunately, the majority of the brachytherapy-induced ED population responds favorably to sildenafil.

Topics: Adenocarcinoma; Aged; Brachytherapy; Erectile Dysfunction; Humans; Iodine Radioisotopes; Male; Middle Aged; Palladium; Penis; Phosphodiesterase Inhibitors; Piperazines; Prostatic Neoplasms; Purines; Radiation Dosage; Radioisotopes; Retrospective Studies; Sildenafil Citrate; Sulfones

The evaluation of potency preservation after treatment of localized prostate cancer with transperineal permanent prostate brachytherapy (PPB) and the efficacy of sildenafil were studied.. This study comprised 482 patients who were able to maintain an erection suitable for intercourse before treatment from a cohort of 1166 patients with clinically localized prostate cancer treated with PPB. All patients have been followed prospectively, and actuarial analysis was performed to assess potency preservation over time. Patients treated with sildenafil were evaluated as to its efficacy.. The median follow-up of this cohort was 34 months (6--92), with a median age of 68 years (47--80). Potency was preserved in 311 of the 482 patients, with a 5-year actuarial potency rate of 52.7%. The 5-year actuarial potency rate for patients treated with PPB as monotherapy was 76%, and, for those treated with combination external beam radiotherapy (EBT) + PPB, 56% (p = 0.08). Patients treated with neoadjuvant androgen deprivation (NAAD) + PPB had a 5-year potency rate of 52%, whereas those with combination EBT + PPB + NAAD had a potency rate of 29% (p = 0.13). Cox regression analysis identified that pretreatment use of NAAD and patient age predicted for impotence (p = 0.0001 and 0.04, respectively). Of 84 patients treated with sildenafil, 52 had a successful outcome (62%). The response to sildenafil was significantly better in those patients not treated with NAAD (p = 0.04).. The actuarial potency rates at 5 years for patients treated with PPB are lower than generally acknowledged, except for those patients treated with PPB as monotherapy. Patients who received sildenafil exhibited improved potency in a majority of cases.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Brachytherapy; Cohort Studies; Combined Modality Therapy; Confounding Factors, Epidemiologic; Erectile Dysfunction; Follow-Up Studies; Humans; Life Tables; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; New York; Piperazines; Proportional Hazards Models; Prospective Studies; Prostatic Neoplasms; Purines; Quality of Life; Radiation Injuries; Radiotherapy, High-Energy; Sildenafil Citrate; Sulfones; Vasculitis